Bing–Neel syndrome

Overview

Bing–Neel syndrome is a rare neurological complication of Waldenström's macroglobulinemia, a type of non-Hodgkin lymphoma characterized by the overproduction of abnormal IgM antibodies. In Bing–Neel syndrome, malignant lymphoplasmacytic cells infiltrate the central nervous system (CNS), leading to a range of neurological symptoms. The syndrome was first described by Jens Bing and Axel Neel in 1936. It can affect both the brain and spinal cord and may occur either at the time of Waldenström’s diagnosis or later in the disease course.

Causes

The underlying cause of Bing–Neel syndrome is the infiltration of the CNS by malignant lymphoplasmacytic cells that originate from Waldenström’s macroglobulinemia. While the exact mechanism that leads these cancerous cells to breach the blood-brain barrier is not fully understood, it is believed that genetic and molecular factors involved in the transformation and migration of these cells play a role. Bing–Neel syndrome is extremely rare, occurring in less than 1% of patients with Waldenström’s macroglobulinemia.

Symptoms

The symptoms of Bing–Neel syndrome are highly variable and depend on the location and extent of CNS involvement. Common signs and symptoms include:

• Headaches

• Cognitive impairment – memory loss, confusion, or personality changes

• Seizures

• Visual disturbances

• Weakness or numbness – particularly in the limbs

• Difficulty walking or coordination problems

• Cranial nerve palsies – such as facial weakness or hearing loss

Symptoms can develop gradually or acutely, and may mimic other neurological conditions, making early diagnosis challenging.

Diagnosis

Diagnosis of Bing–Neel syndrome requires a high index of suspicion in patients with known or suspected Waldenström’s macroglobulinemia who develop neurological symptoms. Diagnostic steps may include:

• Magnetic Resonance Imaging (MRI) – often shows diffuse or nodular lesions in the brain or spinal cord

• Lumbar puncture – cerebrospinal fluid (CSF) analysis may reveal malignant lymphoplasmacytic cells and elevated protein levels

• Flow cytometry and cytology of CSF – to detect clonality and confirm the presence of lymphoma cells

• Brain biopsy – in rare cases where imaging and CSF analysis are inconclusive

• Serum and bone marrow studies – to confirm or reassess Waldenström’s macroglobulinemia

Treatment

Treatment of Bing–Neel syndrome focuses on controlling the CNS infiltration and underlying lymphoplasmacytic lymphoma. Treatment approaches include:

• Systemic chemotherapy – agents such as bendamustine, fludarabine, or rituximab-based regimens

• Intrathecal chemotherapy – direct delivery of drugs like methotrexate or cytarabine into the CSF

• Targeted therapy – including Bruton's tyrosine kinase (BTK) inhibitors like ibrutinib, which can penetrate the blood-brain barrier

• Radiation therapy – used in selected cases with focal CNS involvement

• Supportive care – including corticosteroids to reduce inflammation and symptom management

Choice of treatment depends on patient condition, extent of disease, and prior therapies.

Prognosis

The prognosis of Bing–Neel syndrome varies widely and depends on the extent of CNS involvement, the patient’s response to treatment, and overall health status. Early detection and appropriate therapy can lead to meaningful neurological improvement and disease control. However, due to the aggressive nature of CNS involvement, outcomes can be poor in untreated or advanced cases. Long-term follow-up and monitoring are essential, and newer targeted therapies have shown promise in improving survival and quality of life for affected individuals.